PROJECT SUMMARY/ABSTRACT The applicant, Pankaj Arora, MD is an Assistant Professor of Medicine in the Division of Cardiovascular Disease at University of Alabama at Birmingham. The applicant?s goal is to become an independent investigator in clinical and translational research and advance the understanding of how disorders in the natriuretic peptide (NP) system contribute to the development of hypertension, heart failure and cardiovascular disease. The applicant has shown a prior interest in understanding the genetics, NP system biology and an ability to conduct high-quality patient-oriented research. This Mentored Patient-Oriented Research Career Development Award (K23) describes a five-year plan that will allow the applicant to achieve independence as an investigator, under the primary mentorship of Thomas J. Wang MD, an internationally-recognized leader in the field of NP physiology. The applicant wishes to obtain knowledge and expertise in 4 specific domains: (1) patient-oriented physiologic studies, (2) the pathophysiologic basis of race-related differences in cardiovascular disease susceptibility, (3) exercise physiology, and (4) patient-oriented pharmacologic studies. African-Americans have increased prevalence of cardiovascular disease which contributes to racial disparities in outcomes such as death and hospitalization. NPs are natriuretic and vasodilatory hormones produced by the heart in response to increased wall stress in the atria and ventricles. In preliminary work for this proposal, we found that African-American race is associated with NP deficiency. Little is known about the physiological consequences of the lower resting NP levels found in African-Americans. The current proposal will seek to determine if there exists racial differences in how the heart responds to physiological perturbations such as exercise and beta blockers. The specific aims are (1) To compare the NP response to beta blockers in African- American and white individuals (2) To compare the NP response to exercise in African-American and white individuals. Understanding these differences in release of NPs may have biological and therapeutic importance in the treatment of hypertension and heart failure. The Mentored Patient-Oriented Research Career Development award (K23) will provide Dr. Arora with the necessary time to fully engage in multifaceted, carefully designed patient-oriented research protocols while serving as a means to receive additional formal didactics. During the course of the award period, the applicant will pursue a Master of Science in Public Health in Clinical & Translational Science at UAB?s School of Public Health to advance his skills in patient-oriented research (epidemiology, biostatistics, study design, grant- writing, and leadership courses). UAB?s rich collaborative, interdisciplinary environment with national recognition for community engagement will provide Dr. Arora with a platform to successfully conduct the research proposed in the plan. The proposed studies will prepare the investigator to design and conduct interventional studies (e.g. R01) in specific racial subgroups to personalize existing and novel therapeutics around the NP system.